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Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis
Acute respiratory distress syndrome (ARDS) is an inflammatory process of the lungs that develops primarily in response to pulmonary or systemic sepsis, resulting in a disproportionate death toll in intensive care units (ICUs). Given its role as a critical activator of the inflammatory and innate imm...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453061/ https://www.ncbi.nlm.nih.gov/pubmed/34557198 http://dx.doi.org/10.3389/fimmu.2021.737369 |
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author | Hernández-Beeftink, Tamara Guillen-Guio, Beatriz Rodríguez-Pérez, Héctor Marcelino-Rodríguez, Itahisa Lorenzo-Salazar, Jose M. Corrales, Almudena Prieto-González, Miryam Rodríguez-Pérez, Aurelio Carriedo, Demetrio Blanco, Jesús Ambrós, Alfonso González-Higueras, Elena Casanova, Nancy G. González-Garay, Manuel Espinosa, Elena Muriel, Arturo Domínguez, David de Lorenzo, Abelardo García Añón, José M. Soro, Marina Belda, Javier Garcia, Joe G. N. Villar, Jesús Flores, Carlos |
author_facet | Hernández-Beeftink, Tamara Guillen-Guio, Beatriz Rodríguez-Pérez, Héctor Marcelino-Rodríguez, Itahisa Lorenzo-Salazar, Jose M. Corrales, Almudena Prieto-González, Miryam Rodríguez-Pérez, Aurelio Carriedo, Demetrio Blanco, Jesús Ambrós, Alfonso González-Higueras, Elena Casanova, Nancy G. González-Garay, Manuel Espinosa, Elena Muriel, Arturo Domínguez, David de Lorenzo, Abelardo García Añón, José M. Soro, Marina Belda, Javier Garcia, Joe G. N. Villar, Jesús Flores, Carlos |
author_sort | Hernández-Beeftink, Tamara |
collection | PubMed |
description | Acute respiratory distress syndrome (ARDS) is an inflammatory process of the lungs that develops primarily in response to pulmonary or systemic sepsis, resulting in a disproportionate death toll in intensive care units (ICUs). Given its role as a critical activator of the inflammatory and innate immune responses, previous studies have reported that an increase of circulating cell-free mitochondrial DNA (mtDNA) is a biomarker for fatal outcome in the ICU. Here we analyzed the association of whole-blood mtDNA (wb-mtDNA) copies with 28-day survival from sepsis and sepsis-associated ARDS. We analyzed mtDNA data from 687 peripheral whole-blood samples within 24 h of sepsis diagnosis from unrelated Spanish patients with sepsis (264 with ARDS) included in the GEN-SEP study. The wb-mtDNA copies were obtained from the array intensities of selected probes, with 100% identity with mtDNA and with the largest number of mismatches with the nuclear sequences, and normalized across the individual-probe intensities. We used Cox regression models for testing the association with 28-day survival. We observed that wb-mtDNA copies were significantly associated with 28-day survival in ARDS patients (hazard ratio = 3.65, 95% confidence interval = 1.39–9.59, p = 0.009) but not in non-ARDS patients. Our findings support that wb-mtDNA copies at sepsis diagnosis could be considered an early prognostic biomarker in sepsis-associated ARDS patients. Future studies will be needed to evaluate the mechanistic links of this observation with the pathogenesis of ARDS. |
format | Online Article Text |
id | pubmed-8453061 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84530612021-09-22 Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis Hernández-Beeftink, Tamara Guillen-Guio, Beatriz Rodríguez-Pérez, Héctor Marcelino-Rodríguez, Itahisa Lorenzo-Salazar, Jose M. Corrales, Almudena Prieto-González, Miryam Rodríguez-Pérez, Aurelio Carriedo, Demetrio Blanco, Jesús Ambrós, Alfonso González-Higueras, Elena Casanova, Nancy G. González-Garay, Manuel Espinosa, Elena Muriel, Arturo Domínguez, David de Lorenzo, Abelardo García Añón, José M. Soro, Marina Belda, Javier Garcia, Joe G. N. Villar, Jesús Flores, Carlos Front Immunol Immunology Acute respiratory distress syndrome (ARDS) is an inflammatory process of the lungs that develops primarily in response to pulmonary or systemic sepsis, resulting in a disproportionate death toll in intensive care units (ICUs). Given its role as a critical activator of the inflammatory and innate immune responses, previous studies have reported that an increase of circulating cell-free mitochondrial DNA (mtDNA) is a biomarker for fatal outcome in the ICU. Here we analyzed the association of whole-blood mtDNA (wb-mtDNA) copies with 28-day survival from sepsis and sepsis-associated ARDS. We analyzed mtDNA data from 687 peripheral whole-blood samples within 24 h of sepsis diagnosis from unrelated Spanish patients with sepsis (264 with ARDS) included in the GEN-SEP study. The wb-mtDNA copies were obtained from the array intensities of selected probes, with 100% identity with mtDNA and with the largest number of mismatches with the nuclear sequences, and normalized across the individual-probe intensities. We used Cox regression models for testing the association with 28-day survival. We observed that wb-mtDNA copies were significantly associated with 28-day survival in ARDS patients (hazard ratio = 3.65, 95% confidence interval = 1.39–9.59, p = 0.009) but not in non-ARDS patients. Our findings support that wb-mtDNA copies at sepsis diagnosis could be considered an early prognostic biomarker in sepsis-associated ARDS patients. Future studies will be needed to evaluate the mechanistic links of this observation with the pathogenesis of ARDS. Frontiers Media S.A. 2021-09-07 /pmc/articles/PMC8453061/ /pubmed/34557198 http://dx.doi.org/10.3389/fimmu.2021.737369 Text en Copyright © 2021 Hernández-Beeftink, Guillen-Guio, Rodríguez-Pérez, Marcelino-Rodríguez, Lorenzo-Salazar, Corrales, Prieto-González, Rodríguez-Pérez, Carriedo, Blanco, Ambrós, González-Higueras, Casanova, González-Garay, Espinosa, Muriel, Domínguez, de Lorenzo, Añón, Soro, Belda, Garcia, Villar and Flores https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Hernández-Beeftink, Tamara Guillen-Guio, Beatriz Rodríguez-Pérez, Héctor Marcelino-Rodríguez, Itahisa Lorenzo-Salazar, Jose M. Corrales, Almudena Prieto-González, Miryam Rodríguez-Pérez, Aurelio Carriedo, Demetrio Blanco, Jesús Ambrós, Alfonso González-Higueras, Elena Casanova, Nancy G. González-Garay, Manuel Espinosa, Elena Muriel, Arturo Domínguez, David de Lorenzo, Abelardo García Añón, José M. Soro, Marina Belda, Javier Garcia, Joe G. N. Villar, Jesús Flores, Carlos Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis |
title | Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis |
title_full | Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis |
title_fullStr | Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis |
title_full_unstemmed | Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis |
title_short | Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis |
title_sort | whole-blood mitochondrial dna copies are associated with the prognosis of acute respiratory distress syndrome after sepsis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453061/ https://www.ncbi.nlm.nih.gov/pubmed/34557198 http://dx.doi.org/10.3389/fimmu.2021.737369 |
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